Infants of diabetic mothers have an increased incidence of congenital malformations particularly severe lower limb deformities or sacral agenesis. Although environmental and/or maternal factors related to carbohydrate metabolic imbalance have been suggested as etiologic factors, little is known of the predisposing genetic factors which may be important in this disease. The proposed study will examine the association between the HLA and sacral agenesis. Inheritance patterns, recombinations/crossovers and antigen frequencies will be studied by typing for the HLA-A and B determinants and mixed-lymphocytes-culture testing. In addition, the existence of the pre-diabetic state or chemical diabetes in the parents will be determined by glucose tolerance testing and correlated with the HLA typing data for the known associations of diabetes (B8/BW15) with the HLA system. These studies will permit a better estimate of the true incidence of the diabetic state in sacral agenesis, clarify the role of maternal diabetes in the etiology of this disease, and perhaps provide an approach to prenatal diagnosis and genetic counseling. BIBLIOGRAPHIC REFERENCES: RFA: Diabetes in Pregnancy: Effects on Mothers and Offspring. Vol. 5, No. 22, December 20, 1976.